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Usefulness of Direct Oral Anticoagulants in Adult Congenital Heart Disease

2015; Elsevier BV; Volume: 117; Issue: 3 Linguagem: Inglês

10.1016/j.amjcard.2015.10.062

1879-1913

Claudia Pujol, Anne‐Charlotte Niesert, A. Engelhardt, Patric Schoen, Ekatharina Kusmenkov, David Pittrow, Peter Ewert, Harald Kaemmerer,

Congenital Heart Disease Studies

As thromboembolic events (TEE) are common in adults with congenital heart disease (ACHD), adequate oral anticoagulation for prophylaxis or treatment of TEE is important. Until now, mainly vitamin K antagonists have been used in these patients. The purpose of this study was to provide first data on the use of direct oral anticoagulants in ACHD. This prospective, observational, and longitudinal study included 102 consecutive ACHD, of whom 75 (37 women and 38 men; mean age 50 ± 13 years) could be analyzed. Most common CHD were pre-tricuspid shunts (n = 31; 41%), complex CHD (n = 16; 21%), left heart/aortic valve anomalies (n = 5; 6%), right-sided cardiac/pulmonary artery anomalies (n = 9; 13%), post-tricuspid shunts (n = 3; 4%), and others (n = 11; 15%). Five patients had cyanosis and 3 patients a Fontan circulation. Mean follow-up was 12 ± 11 months. Rivaroxaban was administered in 55 patients, apixaban in 13 and dabigatran in 7 patients for TEE prophylaxis in atrial arrhythmias (n = 57), stroke/transient ischemic attacks (n = 11), deep vein thrombosis (n = 4), pulmonary embolism (n = 1) and atrial thrombi (n = 3). Some patients had >1 indication for adequate oral anticoagulation. CHA2-DS2-VASc score was ≥2 in 23 (31%), and 9 (12%) had a HAS-BLED score ≥2. There were neither thrombotic or major bleeding events nor major side effects. In conclusion, direct oral anticoagulants appear to be safe and effective in ACHD. Long-term follow-up is needed to substantiate these findings. As thromboembolic events (TEE) are common in adults with congenital heart disease (ACHD), adequate oral anticoagulation for prophylaxis or treatment of TEE is important. Until now, mainly vitamin K antagonists have been used in these patients. The purpose of this study was to provide first data on the use of direct oral anticoagulants in ACHD. This prospective, observational, and longitudinal study included 102 consecutive ACHD, of whom 75 (37 women and 38 men; mean age 50 ± 13 years) could be analyzed. Most common CHD were pre-tricuspid shunts (n = 31; 41%), complex CHD (n = 16; 21%), left heart/aortic valve anomalies (n = 5; 6%), right-sided cardiac/pulmonary artery anomalies (n = 9; 13%), post-tricuspid shunts (n = 3; 4%), and others (n = 11; 15%). Five patients had cyanosis and 3 patients a Fontan circulation. Mean follow-up was 12 ± 11 months. Rivaroxaban was administered in 55 patients, apixaban in 13 and dabigatran in 7 patients for TEE prophylaxis in atrial arrhythmias (n = 57), stroke/transient ischemic attacks (n = 11), deep vein thrombosis (n = 4), pulmonary embolism (n = 1) and atrial thrombi (n = 3). Some patients had >1 indication for adequate oral anticoagulation. CHA2-DS2-VASc score was ≥2 in 23 (31%), and 9 (12%) had a HAS-BLED score ≥2. There were neither thrombotic or major bleeding events nor major side effects. In conclusion, direct oral anticoagulants appear to be safe and effective in ACHD. Long-term follow-up is needed to substantiate these findings. Cardiovascular disorders, including thromboembolic events (TEE), are the most common causes of death. As many adults with congenital heart disease (ACHD) are prone to TEE, and morbidity and mortality from these complications are also high, adequate oral anticoagulation (OAC) for prophylaxis or treatment of TEE is of outstanding importance. To date, only data about the use of vitamin K antagonists (VKA) are available in these patients.1Riva N. Lip G.Y. A new era for anticoagulation in atrial fibrillation.Pol Arch Intern Med. 2012; 122: 45-53PubMed Google Scholar Data on the use of novel or direct oral anticoagulants (DOAC) in ACHD are scarce.2Lummert E. Beitrag zur Problematik nicht-kardialer Comorbiditaeten bei Erwachsenen mit angeborenen Herzfehlern. Technical University Munich, Munich2015Google Scholar Therefore, the purpose of this analysis is to provide first real-world experience regarding the anticoagulation management of ACHD using DOACs. A total of 102 ACHD, who attended our specialized department for ACHD, and in whom DOACs had been recommended and/or prescribed, were identified and requested to participate in a prospective observational longitudinal study. The patients were included consecutively in the order that they presented at our institution and were not selected by the physician in any particular way that might influence the results of the study. Written informed consent was obtained from all patients (age ≥18 years) who were taking, had taken, or were proposed to initiate treatment with a DOAC. Exclusion criteria were contraindication for DOACs (e.g., mechanical prosthetic heart valves), lack of cognitive competency to understand and/or fill in the questionnaire, and refusal to consent. A detailed medical questionnaire was mailed to all patients to determine their recent clinical and treatment status and follow-up information. The patients themselves filled in the questionnaire. Patients who did not return or complete the questionnaire were sent a second questionnaire. If the second questionnaire was not returned or completed, attempts were made to contact the patient by phone. The treating physicians in our institution completed the cardiac diagnoses, medical treatment, the medical history, details of previous cardiac interventions or operations, and the clinical assessment. Medical records were obtained from all participating patients and reviewed for anatomic characteristics of respective cardiac anomalies, if applicable. The questionnaire included questions regarding clinical aspects, including age, gender, indication, type and doses of DOAC, previous OAC, renal or liver disease, cardiovascular risk factors, alcohol intake, relevant co-medication and bleeding disorders, drug side effects (Figure 2), and bleeding complications according to International Society on Thrombosis and Haemostasis, thrombotic complications, drug discontinuation, or dose reduction.3Schulman S. Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.J Thromb Haemost. 2005; 3: 692-694Crossref PubMed Scopus (3150) Google Scholar CHADS2 score, CHA2-DS2-VASc score, and HAS-BLED score were calculated. Patients were classified according to the underlying CHD and assigned to 1 of 6 major groups, including complex CHD (group 1), obstruction of the left ventricle/anomalies of the aortic valve (group 2), obstruction of the right ventricle/anomalies of pulmonary valve or pulmonary artery (group 3), post-tricuspid shunts (group 4), pre-tricuspid shunts (group 5), and other congenital heart anomalies (group 6) (Table 1). Patients with Fontan circulation and severe chronic cyanosis were analyzed separately. A total of 3 patients (1 woman) had a Fontan circulation. There were 5 patients with severe cyanosis (3 women). Diagnoses were double inlet ventricle (2), Ebstein's anomaly (2), and atrial septal defect (1).Table 1Patient demographics (n = 75): type, number and percentage of congenital heart anomaliesCongenital Heart DiseasesN (%)Hypoplastic left heart2 (3%)Double inlet left ventricle2 (3%)Double outlet right ventricle (univentricular repair)1 (1%)Transposition of great arteries10 (13%)Congenital corrected transposition of great arteries1 (1%)Aortic coarctation1 (1%)Aortic stenosis2 (3%)Subaortic stenosis1 (1%)Aortic regurgitation1 (1%)Tetralogy of Fallot5 (7%)Double outlet right ventricle/Fallot-type2 (3%)Pulmonary atresia with ventricular septal defect2 (3%)Ventricular septal defect2 (3%)Patent ductus arteriosus1 (1%)Patent foramen ovale9 (12%)Atrial septal defect22 (29%)Ebstein's anomaly6 (8%)Aneurysm of Aorta1 (1%)Ectasia great arteries2 (3%)Others2 (3%) Open table in a new tab The study was approved by the institutional ethics committee. Statistical analyses were made using SPSS for Windows, version 22.0 (IBM Corp, Armonk, NY). The presentation of the metric variables was performed as means and medians, and the scattering measurements expressed as standard deviations and quartiles. Categorical or nominal data were expressed as absolute and relative frequency. A total of 102 patients in whom DOACs had been recommended and/or prescribed were identified and included in the study. Sixteen patients were not considered in the analysis as follow-up data were not available yet. Another 11 patients did not receive the proposed medication: in 8 patients, the family physician did not implement the suggested treatment and 3 patients rejected the therapy (Figure 1). Ultimately, 75 patients were included in the analysis (n = 38 men; n = 37 women). Patient age was between 22 and 74 years (median 51 years; mean 50 ± 13 years). A total of 18 patients (24%) were between 20 and 40 years, and 41 patients (55%) were between 41 and 60 years. The remaining patients (16 patients, 21%) were >60 years. Overall, complex CHD was present in 21% (n = 16) of patients, obstruction of the left ventricle/anomalies of the aortic valve in 6% (n = 5), obstruction of the right ventricle/anomalies of pulmonary valve or pulmonary artery in 13% (n = 9), post-tricuspid shunts in 4% (n = 3), pre-tricuspid shunts in 41% (n = 31), and other defects in 15% (n = 11). There were 5 patients (7%) with chronic cyanosis (Table 1). There were 17 patients (23%) with previous corrective cardiac surgery and 23 patients (31%) with palliative surgery. Re-operation was detected in 21 patients (28%). A primarily curative percutaneous interventional treatment had been performed in 30 patients (40%). Finally, 5 patients (7%) had neither a cardiac intervention nor a surgical procedure. Cardiovascular risk factors, previous disorders, and concomitant medication with known potential for interaction with DOACs are given in Table 2.Table 2Cardiovascular risk factors, previous disorders and concomitant medication with known potential for interaction with DOACEpidemiological AspectsN (%)Cardiovascular risk factors Arterial hypertension7 (9%) Diabetes mellitus7 (9%) Hyperlipidemia12 (16%) Ischemic heart disease8 (11%) Nicotine consumption:Smoker20 (27%)Ex-smoker2 (3%) Alcohol consumption17 (23%)Previous disorders TIA/Stroke15 (20%) Thrombosis7 (9%) Pulmonary thromboembolism1 (1%) Bleeding5 (7%) Chronic liver disease3 (4%) Chronic renal disease1 (1%)Concomitant medication Nonsteroidal anti-inflammatory drugs7 (9%) Oral contraceptives5 (7%) Antidepressants6 (8%) Open table in a new tab Anti-Xa antagonists were prescribed in 68 patients and thrombin antagonists in 7 patients. Rivaroxaban was the most commonly used drug (n = 55, 73%), followed by apixaban (n = 13, 17%) and dabigatran (n = 7, 9%) (Figure 1). Main indications of DOAC were TEE prophylaxis in atrial arrhythmias (n = 57 patients; 76%) and stroke/TIA (n = 15; 20%). Other indications were prophylaxis after deep vein thrombosis (n = 4, 5%), pulmonary embolism (n = 1; 1%), and atrial thrombi (n = 3; 4%) (1 patient with Fontan circulation, 1 with thrombus adhered to an ASD-Occluder, and 1 with thrombus on a pacemaker electrode). There were 10 patients with 2 indications for OAC: stroke/TIA and atrial arrhythmias (Table 3).Table 3Indications for direct oral anticoagulants (DOAC), diagnoses and medication usedIndicationsN (%)Diagnoses (N)DabigatranN (%)RivaroxabanN (%)ApixabanN (%)Atrial arrhythmias57 (76%)Hypoplastic left heart (2)Double inlet left ventricle (1)Transposition great arteries (10)Congenitally corrected TGA (1)Aortic coarctation (1)Aortic stenosis (2)Subaortic stenosis (1)Tetralogy of Fallot (2)DORV - Fallot type (3)Pulmonary atresia - VSD (2)Ventricular septal defect (2)Patent ductus arteriosus (1)Patent foramen ovale (5)Atrial septal defect (17)Ebstein's anomaly (4)Aortic aneurysm (1)Ectasia of great arteries (1)Other (1)4 (7%)44 (77%)9 (16%)Stroke/TIA15 (20%)Hypoplastic left heart (1)Transposition great arteries (1)Tetralogy of Fallot (1)Patent foramen ovale (8)Atrial septal defect (3)Ebstein's anomaly (1)3 (20%)10 (67%)2 (13%)Deep vein thrombosis4 (5%)Patent foramen ovale (1)Atrial septal defect (1)Ebstein's anomaly (1)Ectasia of the great arteries (1)1 (25%)3 (75%)-Pulmonary embolism1 (1%)Ebstein's anomaly (1)-1(100%)-Atrial thrombus3 (4%)Atrial septal defect (1)Aortic regurgitation (1)Double outlet right ventricle (1)-1 (33%)2 (67%)DORV = double outlet right ventricle; TGA = transposition of the great arteries; VSD = ventricular septal defect. Open table in a new tab DORV = double outlet right ventricle; TGA = transposition of the great arteries; VSD = ventricular septal defect. The CHA2-DS2-VASc score in all included patients was 0 in 40 patients (53%), 1 in 12 patients (16%), 2 in 7 patients (9%), 3 in 12 patients (16%), 4 in 1 patient (1%), 5 in 2 patients (3%) and 7 in 1 patient (1%). A CHADS2 score ≥2 was present in 15 patients (20%). The HAS-BLED score was 0 in 54 patients (72%), 1 in 12 patients (16%), 2 in 7 patients (9%), and 3 in 2 patients (3%). The mean follow-up period was 12 ± 11 months (range 1 to 61 months). Most patients did not report relevant side effects from DOAC (Figure 2) and no major bleeding was reported. Temporary interruption of DOAC was reported in 3 patients: 2 patients because of bleeding (1 rupture of muscle fibers and another because of hematuria) and 1 because of an imminent major operation. One patient discontinued treatment because of allergic reaction. Minor bleeding events, including intermittent epistaxis, bleeding after minor injuries or dental manipulation, or predisposition to hematoma, were reported in 47%. The 3 patients with Fontan circulation tolerated DOAC very well and no major bleeding or thromboembolic complications were reported. None of the 5 cyanotic patients developed significant bleeding complications or a TEE. This analysis provides first real-world experiences concerning the use of DOACs in ACHD. The study, including 75 adults with different types and severity levels of CHD, demonstrates that main indication for anticoagulation in this group is prevention of TEE secondary to atrial arrhythmias and that DOAC treatment is effective, side effects are mild, and complications seldom. Although mortality from CHD has decreased considerably during the last decades, morbidity is still high and co-morbidities, including TEE, complicate the natural history.2Lummert E. Beitrag zur Problematik nicht-kardialer Comorbiditaeten bei Erwachsenen mit angeborenen Herzfehlern. Technical University Munich, Munich2015Google Scholar, 4Kaemmerer H. Hess J. Congenital heart disease. Transition from adolescence to adulthood.Internist (Berl). 2009; 50: 1221-1222Crossref PubMed Scopus (15) Google Scholar, 5Perloff J.K. Warnes C.A. Challenges posed by adults with repaired congenital heart disease.Circulation. 2001; 103: 2637-2643Crossref PubMed Scopus (168) Google Scholar A recent study on 800 ACHD could demonstrate that 22% of them were on oral anticoagulation, nearly always VKA.2Lummert E. Beitrag zur Problematik nicht-kardialer Comorbiditaeten bei Erwachsenen mit angeborenen Herzfehlern. Technical University Munich, Munich2015Google Scholar In the last years, the direct thrombin inhibitor dabigatran (Pradaxa, Boehringer Ingelheim) and factor Xa inhibitors (rivaroxaban [Xarelto], Bayer HealthCare; apixaban [Eliquis], Bristol-Myers Squibb; and edoxaban [Lixiana], Daiichi Sankyo) have been introduced for prevention and/or treatment of venous and arterial TEE. Despite the encouraging efficacy and safety profile, only scarce data are available on the use in ACHD. DOACs have major pharmacologic advantages compared with VKA, including fast begin and offset of action, fewer drug and food interactions, and a more predictable pharmacokinetic, removing the requirement for routine coagulation monitoring. Advantages are counterbalanced by concerns regarding dosing in some populations (e.g., renal dysfunction) and superior drug costs compared with VKA. Moreover, currently, only limited experience with prothrombin complex concentrates and other agents for reversal of anticoagulation is available. Quite recently for idarucizumab, an antidote that can specifically neutralize the effect of dabigatran within minutes, a priority review designation has been granted by the Food and Drug Administration, and antidotes for the other DOACs are currently in development too. In the medical care of ACHD, TEE and OAC are central issues. In our patients, indication for DOAC was prevention of TEE due to atrial arrhythmias in 76%, compatible with that cardiac arrhythmias are a main cause of hospitalization in ACHD. Up to 20% of ACHD develop supraventricular arrhythmias during their live, increasing the risk for TEE, heart failure, and death from cardiac causes.6Engelfriet P. Boersma E. Oechslin E. Tijssen J. Gatzoulis M.A. Thilén U. Kaemmerer H. Moons P. Meijboom F. Popelová J. Laforest V. Hirsch R. Daliento L. Thaulow E. Mulder B. 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Frequency of late recurrence of intra-atrial reentry tachycardia after radiofrequency catheter ablation in patients with congenital heart disease.Am J Cardiol. 2003; 92: 879-881Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 10Bédard E. Shore D.F. Gatzoulis M.A. Adult congenital heart disease: a 2008 overview.Br Med Bull. 2008; 85: 151-180Crossref PubMed Scopus (51) Google Scholar, 11Rädle-Hurst T. Abdul-Khaliq H. Cardiac arrhythmia in adults with congenital heart disease.Intensivmed und Notfallmedizin. 2011; 48: 21-26Crossref Scopus (2) Google Scholar Cerebrovascular events were the second most frequent indication for DOACs in our study. Ten of 15 ACHD with previous stroke also had atrial arrhythmias. Incidence and prevalence of stroke in ACHD registers are 10% to 100% higher compared with the general population.6Engelfriet P. Boersma E. Oechslin E. Tijssen J. Gatzoulis M.A. Thilén U. Kaemmerer H. Moons P. Meijboom F. Popelová J. Laforest V. Hirsch R. Daliento L. 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Gatzoulis M.A. Percutaneous patent foramen ovale occlusion: current evidence and evolving clinical practice.Int J Cardiol. 2013; 169: 238-243Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar At particular risk are ACHD with pulmonary arterial hypertension, Eisenmenger syndrome, tricuspid stenosis, or Ebstein's anomaly. In our study, the most common shunt lesions were ASD and PFO. The optimal treatment of such a PFO is still controversial, but as long as the defect remains unclosed, anticoagulation may be justified in precarious patients.15Khan A.R. Bin Abdulhak A.A. Sheikh M.A. Khan S. Erwin P.J. Tleyjeh I. Khuder S. Eltahawy E.A. Device closure of patent foramen ovale versus medical therapy in cryptogenic stroke: a systematic review and meta-analysis.JACC Cardiovasc Interv. 2013; 6: 1316-1323Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar Currently, the definitive role of DOACs in the prevention and treatment of cerebrovascular disease remains unclear. Clinical trials are required to study the short-term and long-term use of DOACs in patients with stroke and a patent foramen ovale. At risk for venous TEE are also ACHD after implantation of a pacemaker or an implantable cardioverter defibrillator.16Khairy P. Landzberg M.J. Gatzoulis M.A. Mercier L.A. Fernandes S.M. Côté J.M. Lavoie J.P. Fournier A. Guerra P.G. Frogoudaki A. Walsh E.P. Dore A. Transvenous pacing leads and systemic thromboemboli in patients with intracardiac shunts: a multicenter study.Circulation. 2006; 113: 2391-2397Crossref PubMed Scopus (225) Google Scholar, 17Kaemmerer H. Fratz S. Braun S.L. Koelling K. Eicken A. Brodherr-Heberlein S. Pietrzik K. Hess J. Erythrocyte indexes, iron metabolism, and hyperhomocysteinemia in adults with cyanotic congenital cardiac disease.Am J Cardiol. 2004; 94: 825-828Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar TEE are of outstanding importance and one of the main causes of death in any type of Fontan circulation due to atrial arrhythmias, venous stasis, protein-losing enteropathy, and/or coagulation disorders associated with liver disease.18Coon P.D. Rychik J. Novello R.T. Ro P.S. Gaynor J.W. Spray T.L. Thrombus formation after the Fontan operation.Ann Thorac Surg. 2001; 71: 1990-1994Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar, 19Khairy P. Fernandes S.M. Mayer J.E. Triedman J.K. Walsh E.P. Lock J.E. Landzberg M.J. Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery.Circulation. 2008; 117: 85-92Crossref PubMed Scopus (746) Google Scholar, 20Balling G. Vogt M. Kaemmerer H. Eicken A. Meisner H. Hess J. Intracardiac thrombus formation after the Fontan operation.J Thorac Cardiovasc Surg. 2000; 119: 745-752Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar, 21Canter C.E. Preventing thrombosis after the Fontan procedure not there yet.J Am Coll Cardiol. 2011; 58: 652-653Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar We included 3 patients with Fontan circulation in our study, but neither major bleeding nor thrombotic complications occurred under DOAC. Cyanotic cardiac anomalies may increase the risk for TEE, particularly because of a high hematocrit, hyperviscosity, therapeutic phlebotomies, iron deficiency, and atrial arrhythmias.22Ammash N. Warnes C.A. Cerebrovascular events in adult patients with cyanotic congenital heart disease.J Am Coll Cardiol. 1996; 28: 768-772Abstract Full Text PDF PubMed Google Scholar, 23Perloff J.K. Marelli A.J. Miner P.D. Risk of stroke in adults with cyanotic congenital heart disease.Circulation. 1993; 87: 1954-1959Crossref PubMed Scopus (129) Google Scholar The 5 patients with chronic cyanosis in our cohort did not report more side effects, bleeding, or thrombotic complications than other patients. The latter applied also for the 18 ACHD on concomitant medication (e.g., contraceptives) with potential for interaction with DOAC that may increase the TEE risk.24Jick S.S. Kaye J.A. Russmann S. Jick H. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol.Contraception. 2006; 73: 223-228Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar, 25Heinemann L. Dinger J. Range of published estimates of venous thromboembolism incidence in young women.Contraception. 2007; 75: 328-336Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar Although so many ACHD require OAC, scientific data or evidence-based treatment algorithms considering the adequate use of DOACs for preventing TEE are lacking for this heterogeneous and unique population. Anyhow, the existing treatment recommendations from general cardiology cannot be transmitted directly to ACHD. Exception of the rule is that patients with mechanical heart valve prosthesis should not be treated with DOACs.26Eikelboom J.W. Connolly S.J. Brueckmann M. Granger C.B. Kappetein A.P. Mack M.J. Blatchford J. Devenny K. Friedman J. Guiver K. Harper R. Khder Y. Lobmeyer M.T. Maas H. Voigt J.-U. Simoons M.L. van de Werf F. Dabigatran versus warfarin in patients with mechanical heart valves.N Engl J Med. 2013; 369: 1206-1214Crossref PubMed Scopus (1006) Google Scholar The risk of stroke and bleeding is assessed in general cardiology by scoring systems.27Camm J. Lip G.Y. De Caterina R. Savelieva I. Atar D. Hohnloser S.H. Hindricks G. Kirchhof P. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association.Eur Heart J. 2012; 33: 2719-2747Crossref PubMed Scopus (3093) Google Scholar The CHADS2 and the CHA2-DS2-VASc scores may predict the annual stroke risk in atrial fibrillation, and the HAS-BLED score estimates the 1-year risk for major bleeding in atrial fibrillation. In ACHD, the applicability and potential benefit of these scores are uncertain. Being aware that these scores are validated in atrial fibrillation, the risk scores were calculated for all included ACHD in the present study to get a first impression about their TEE and bleeding risk. Our hypothesis that the CHA2-DS2-VASc and HAS-BLED scores can be used for risk stratification in ACHD is supported by most recent data from a Dutch study assessing thrombotic and bleeding events in adults with atrial arrhythmias and congenital heart disease.28Heidendael J. Bokma J. de Groot J. Koolbergen D. Mulder B. Bouma B. Weighing the risks: thrombotic and bleeding events in adults with atrial arrhythmias and congenital heart disease.Int J Cardiol. 2015; 186: 315-320Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 29Jensen S. Idorn L. Norager B. Vejlstrup N. Sondergaard L. Anticoagulation in adults with congenital heart disease: the who, the when and the how?.Heart. 2015; 101: 424-429Crossref PubMed Scopus (29) Google Scholar According to CHA2-DS2-VASc, our population had a low risk of thromboembolic stroke in almost 70% of cases. Nevertheless, they received OAC, taking into account clinical particularities of the congenital anomaly and the treatment status, particularly in patients with previous intracardiac repair, cyanosis, Fontan circulation, or a systemic right ventricle.29Jensen S. Idorn L. Norager B. Vejlstrup N. Sondergaard L. Anticoagulation in adults with congenital heart disease: the who, the when and the how?.Heart. 2015; 101: 424-429Crossref PubMed Scopus (29) Google Scholar Anyhow, our population is not well depicted in the CHA2-DS2-VASc score as Bouchardy et al8Bouchardy J. Therrien J. Pilote L. Ionescu-Ittu R. Martucci G. Bottega N. Marelli A.J. Atrial arrhythmias in adults with congenital heart disease.Circulation. 2009; 120: 1679-1686Crossref PubMed Scopus (313) Google Scholar published that ACHD with atrial arrhythmias have twice the risk of stroke than general population. Moreover, in 72% of our patients, HAS-BLED values were ≤1, displaying a low bleeding risk, perhaps because of the young age and a low prevalence of arterial hypertension and renal and liver disease. Accordingly, severe bleeding complications were not reported in our cohort during follow-up. In only 3 patients, DOAC therapy was temporarily discontinued and in 1 patient stopped because of an allergic reaction. There were no thrombotic complications and only minor adverse events. A remarkable observation was that in almost 8% of patients DOACs were not prescribed by the general practitioner although recommended by the ACHD specialist. This is surprising as usually recommendations given by a tertiary care center are accepted. This may be because of a lack of experience with these substances, fear of intractable bleeding, a vague approval status (i.e., "off-label use"), or fear of compensation claims from the insurance provider because of uneconomic prescription. Our study has inherent limitations. As it is not a randomized controlled trial, our results are for sure biased. Moreover, the number of patients included is currently not high compared with the major number of ACHD who need oral anticoagulation. As the time of follow-up is short, the low number of complications might also be influenced by this. A verification of the reported side effects goes beyond the aims of the study and must be left to further specific studies. Finally, some anomalies, prone to thrombotic events because of cyanosis or Fontan circulation, are underrepresented in the study. The authors have no conflicts to disclosure. Dr. Kaemmerer has received honoraria for lectures from Bayer HealthCare (Germany), Boehringer Ingelheim (Germany), and Pfizer (Germany). Dr. Pittrow has received speaker fees or honoraria for consultations from Actelion, Bayer HealthCare (Germany), Boehringer Ingelheim (Germany), Novartis (Germany), and Pfizer (Germany). All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. The views expressed in this publication are those of the authors and do not necessarily represent those of the funder.